Usher Syndrome: Genetics of a Human Ciliopathy

Usher syndrome (USH) is an autosomal recessive syndromic ciliopathy characterized by sensorineural hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. There are three clinical types depending on the severity and age of onset of the symptoms; in addition, ten genes are reported to be causative of USH, and six more related to the disease. These genes encode proteins of a diverse nature, which interact and form a dynamic protein network called the “Usher interactome”. In the organ of Corti, the USH proteins are essential for the correct development and maintenance of the structure and cohesion of the stereocilia. In the retina, the USH protein network is principally located in the periciliary region of the photoreceptors, and plays an important role in the maintenance of the periciliary structure and the trafficking of molecules between the inner and the outer segments of photoreceptors. Even though some genes are clearly involved in the syndrome, others are controversial. Moreover, expression of some USH genes has been detected in other tissues, which could explain their involvement in additional mild comorbidities. In this paper, we review the genetics of Usher syndrome and the spectrum of mutations in USH genes. The aim is to identify possible mutation associations with the disease and provide an updated genotype–phenotype correlation.     

Effects of hydroelectric scheme on fluvial ecosystems within the Spanish Pyrenees

The effects on faunal communities of a high head, low capacity hydroelectric power project are evaluated for the River Cinca, a Pyrenean tributary of the River Ebro (North East of Spain). The macrobenthic fauna of the regulated Cinca river is compared with the unregulated River Ara. Colder summer water temperatures in the River Cinca are shown to have caused a reduction in species richness of the macrobenthic community as a consequence of the elimination of thermophilous species. Reduced temperatures may also explain the lower growth rate and productivity of the trout populations. Sudden flow fluctuations caused by hydropower generation influence the downstream macrobenthic communities; their populations are less abundant (reduction in densities and biomass) and their structure is less diverse. Although trout fisheries do not seem to be directly affected by sudden flow fluctuations, the limitation of their food resources (benthos), has reduced trout production and turnover ratio.     

OPERA: a novel method to reduce ghost and aliasing artifacts

Objective

A method for Orthogonal Phase Encoding Reduction of Artifact (OPERA) was developed and tested.

Materials and methods

Because the position of ghosts and aliasing artifacts is predictable along columns or rows, OPERA combines the intensity values of two images acquired using the same parameters, but with swapped phase-encoding directions, to correct the artifacts. Simulations and phantom experiments were conducted to define the efficacy, robustness, and reproducibility. Clinical validation was performed on a total of 1003 images by comparing the OPERA-corrected images and the corresponding image standard in terms of Signal-to-Noise Ratio (SNR) and Contrast-to-Noise Ratio (CNR). The method efficacy was also rated using a Likert-type scale response by two experienced independent radiologists using a single-blinded procedure.

Results

Simulations and phantom experiments demonstrated the robustness and effectiveness of OPERA in reducing artifacts strength. OPERA application did not significantly change the SNR [+?4.16%; inter-quartile range (IQR): 2.72–5.01%] and CNR (+?4.30%; IQR: 2.86–6.04%) values. The two radiologists observed a total of 893 original images with artifacts (89.03% of the total images), a reduction in the perceived artifacts of 82.0% and 83.9% (p?<?0.0001), and an improvement in the perceived SNR (82.8% and 88.5%; K?=?0.714) and perceived CNR (86.9–88.9%; K?=?0.722).

Discussion

The study demonstrated that OPERA reduces MR artifacts and improves the perceived image quality.

     

CT and MRI Imaging of Theranostic Bimodal Fe3O4@Au NanoParticles in Tumor Bearing Mice

Gold-containing nanoparticles are proven to be an effective radiosensitizer in the radiotherapy of tumors. Reliable imaging of nanoparticles in a tumor and surrounding normal tissues is crucial both for diagnostics and for nanoparticle application as radiosensitizers. The Fe₃O₄ core was introduced into gold nanoparticles to form a core/shell structure suitable for MRI imaging. The aim of this study was to assess the in vivo bimodal CT and MRI enhancement ability of novel core/shell Fe₃O₄@Au theranostic nanoparticles. Core/shell Fe₃O₄@Au nanoparticles were synthesized and coated with PEG and glucose. C57Bl/6 mice bearing Ca755 mammary adenocarcinoma tumors received intravenous injections of the nanoparticles. CT and MRI were performed at several timepoints between 5 and 102 min, and on day 17 post-injection. Core/shell Fe₃O₄@Au nanoparticles provided significant enhancement of the tumor and tumor blood vessels. Nanoparticles also accumulated in the liver and spleen and were retained in these organs for 17 days. Mice did not show any signs of toxicity over the study duration. These results indicate that theranostic bimodal Fe₃O₄@Au nanoparticles are non-toxic and serve as effective contrast agents both for CT and MRI diagnostics. These nanoparticles have potential for future biomedical applications in cancer diagnostics and beyond.     

Stable and transient subharmonic emissions from isolated contrast agent microbubbles

Ultrasound contrast agents (UCAs) have been widely studied in recent years in order to improve and develop new, sophisticated imaging techniques for clinical applications. In order to improve the understanding of microbubble-ultrasound interactions, an acoustic dynamic characterization of UCA microbubble behavior was performed in this work using a high frame-rate acquiring and processing system. This equipment is connected to a commercial scanner that provides RF beam-formed data with a frame-rate of 30 Hz. Acquired RF sequences allows us to follow the dynamics of cavitation mechanisms in its temporal evolution during different insonifying conditions. The experimental setup allowed us to keep the bubbles free in a spatial region of the supporting medium, thus avoiding boundary effects that can alter the ultrasound field and the scattered echo from bubbles. The work focuses on the study of subharmonic emission from an isolated bubble of contrast agent. In particular, the acoustic pressure threshold for a subharmonic stable emission was evaluated for a subset of 50 microbubbles at 3.3 MHz and at 5 MHz of insonation frequencies. An unexpected second pressure threshold, which caused the stand still of the subharmonic emission, was detected at 3.3 MHz and 5 MHz excitation frequencies. A transient subharmonic emission, which is hypothesized as being related to the formation of new free gas bubbles, was detected during the ultrasound-induced destruction of microbubbles. An experimental procedure was devised in order to investigate these behaviors and several sequences of RF echo signals and the related spectra, acquired from an isolated bubble in different insonation conditions, are presented and discussed in this paper.     

Comparison of mesenchymal stem cell proliferation and differentiation between biomimetic and electrochemical coatings on different topographic surfaces

The hypothesis for this study was that there is no difference in mesenchymal stem cells (MSCs) proliferation and osteogenic differentiation between calcium-phosphate (CaP) coatings with different crystal size deposited on different topographic surfaces of metal discs. Polished (P) and sand-blasted (SB) tantalum and TiAl6V4 discs were CaP coated by three methods—biomimetic (BioM), electrochemical at 20 mA/cm² and at 6.5 mA/cm²—and cultured with MSCs. At days 4, 7 and 14, cell proliferation—alamarBlue^® activity and DNA quantification—and differentiation down the osteogenic lineage—ALP activity normalised per amount of DNA and SEM (morphology)—were analysed. Results showed that MSCs proliferated more when cultured on the nano-sized BioM coatings compared to uncoated and electrochemically coated discs. MSCs also proliferated more on P surfaces than on SB and or electrochemical coatings. All the coatings induced osteogenic differentiation, which was greater on electrochemical coatings and SB discs.     

Toxicity assessment of nano‐TiO2 in Apis mellifera L., 1758: histological and immunohistochemical assays

The aim of this study was to evaluate the toxicity of titanium dioxide nanoparticles (TiO₂NPs) by short‐term toxicity tests in Apis mellifera, considered an excellent bioindicator organism mainly due to its sensitivity. Bees have been exposed to several concentrations of TiO₂NPs (1 × 10^?3, 1 × 10^?4, 1 × 10^?5, 1 × 10^?6 mg/10 ml) for 10 days. Morphostructural and histological assays were done on gut and honey sac. The research of exposure biomarkers like metallothioneins 1 (MT1) and Heat Shock Protein 70 (HSP70) was performed to verify if a detoxification mechanism has been activated in the exposed animals. No histological alteration on the epithelium of the gut and honey sac were observed in exposed samples. A significant positivity for anti‐MT1 antibody was observed only in the honey sac cells. A weak positivity for HSP70 was observed in both structures analyzed. In several studies have shown the non‐toxicity of TiO₂NPs on other model organisms, in our study, titanium dioxide nanoparticles was proven to be highly toxic at the highest concentration tested (100% of lethality to 1 × 10^?3 mg/10 ml) and moderately toxic at lower concentrations. Honey bees proved to be excellent models for study of NPs toxicity and for monitoring environment.     

Human neuronal nicotinic receptors

Nicotine is a very widely used drug of abuse, which exerts a number of neurovegetative, behavioural and psychological effects by interacting with neuronal nicotinic acetylcholine receptors (NAChRs). These receptors are distributed widely in human brain and ganglia, and form a family of ACh-gated ion channels of different subtypes, each of which has a specific pharmacology and physiology. As human NAChRs have been implicated in a number of human central nervous system disorders (including the neurodegenerative Alzheimer's disease, schizophrenia and epilepsy), they are suitable potential targets for rational drug therapy. Much of our current knowledge about the structure and function of NAChRs comes from studies carried out in other species, such as rodents and chicks, and information concerning human nicotinic receptors is still incomplete and scattered in the literature. Nevertheless, it is already evident that there are a number of differences in the anatomical distribution, physiology, pharmacology, and expression regulation of certain subtypes between the nicotinic systems of humans and other species. This review will attempt to survey the major achievements reached in the study of the structure and function of NAChRs by examining the molecular basis of their functional diversity viewed mainly from pharmacological and biochemical perspectives. It will also summarize our current knowledge concerning the structure and function of the NAChRs expressed by other species, and the newly discovered drugs used to classify their numerous subtypes. Finally, the role of NAChRs in behaviour and pathology will be considered.     

Features of obtaining an effective catalyst for synthesis of carbon nanostructured materials

Abstract

In the present paper, the features of obtaining a metal oxide Fe–Co/Al₂O₃ catalyst for the synthesis of carbon nanostructured materials through thermal decomposition are considered. It was experimentally proved that the temperature and duration of the stage of thermal decomposition of the initial components solution significantly affect the catalyst activity in the synthesis of carbon nanostructured materials by the CVD method. It was found that controlling the mode parameters of the thermal decomposition of the initial components solution of the Fe–Co/Al₂O₃ catalyst, one can not only obtain a catalyst with the required characteristics but also directionally synthesize carbon nanostructured materials over the resulting catalytic systems. During the experiments, rational modes for the implementation of the method for producing catalysts were determined, allowing to form a metal oxide system with a specific surface area of 108?m²/g, the use of which in the synthesis of carbon nanostructured materials leads to the formation of multi-walled carbon nanotubes with an external diameter of 30?nm.     

Degradation of fullerene C60 by human myeloperoxidase and some reaction products

Abstract

The biodegradation of the fullerene molecule C₆₀ under the action of the human myeloperoxidase enzyme accompanied by a complete loss of the topology of the fullerene core. Analysis of this reaction mixture using UV and FTIR spectroscopy, chromatographic and mass spectrometry methods showed that the degradation proceeds without the formation of significant amounts of hydroxylated compounds. Among other intermediate compounds aromatic compounds were detected.